In the past few years, combinatorial chemistry has been recognised as a very useful tool for the synthesis of large numbers of different compounds in a relatively short period of time. This gave an enormous impetus to the research relating to the development of reaction conditions suitable for combinatorial chemistry, and in particular, for solid phase organic chemistry (SPOC). For instance, there is a continuous search for new linkers.
Various linkers are known to be useful in SPOC. Often the choice of linker depends on the specific requirements of the particular type of organic reactions to be performed. Thus, there are acid-sensitive, base-sensitive, nucleophilic-sensitive, electrophilic sensitive, photosensitive, oxidation sensitive or reduction sensitive types of linkers. Also selectively cleavable linkers may be employed. Combinations of such linkers may be used to allow sequential cleaving from a solid support.
A highly important class of linkers are those cleavable under mild, neutral conditions, thus allowing the use and production of complex and sensitive molecules. The application of fluoride induced cleavage offers a mild, essentially neutral, alternative for photolytic, basic or acidic cleavage techniques. Linkers, suitable for this type of cleavage, are e.g. silicium-based linkers. A number of such linkers have already been described. However, many suffer from (technical) drawbacks, such as the fact that they have to be attached to the ligand molecule prior to their attachment to the support (Tetrahedron Lett. 1987, 28, 4105; J.Org.Chem. 1995, 60, 6006; J.Org.Chem. 1996, 61, 6498) and/or a lengthy synthesis (Tetrahedron Lett. 1998, 39, 897; J.Org.Chem. 1988, 53, 5240). Other reported silicium-based linkers (Tetrahedron Lett. 1997, 38, 8287) are significantly less stable towards acids than the linkers of the present invention.